Device for applying a pulsating pressure to a local region of the body and applications thereof

ABSTRACT

The present invention generally relates to a device for applying a pulsating pressure to a local region of the body and applications thereof. The device may be used to increase the blood flow in a local region of the body, and in preferred embodiments provides a device for regulating the core body temperature of a patient.

FIELD OF THE INVENTION

The present specification relates to a device for applying a pulsatingpressure to a local region of the body and applications thereof. Thedevice may be used to increase the blood flow in a local region of thebody, and in preferred embodiments provides a device for regulating thecore body temperature of a patient.

BACKGROUND OF THE INVENTION

The application of pressure and/or thermal energy is often used to treatvarious medical conditions.

It is known to treat oedema by applying pressure to the limb with theoedema. For example, it is known to immerse a limb in a chamber filledwith mercury in a flexible bag. Pressure is applied via the chamber ofmercury to treat the oedema. More recently an improvement to this systemwas described in U.S. Pat. No. 4,648,392, to reduce the amount ofmercury required in the chamber.

The combined application of pressure and temperature is taught in U.S.Pat. No. 5,074,285 for the treatment of sporting injuries such asbruising and muscle stiffness. In that system, thermal sources, whichcould be hot or cold, are introduced into pockets close to the wearersskin and pressure is applied to a series of air pockets arranged alongthe limb that are designed to apply a pressure-gradient repeatedly tothe limb.

Hypothermia is a condition resulting from a drop in body temperature andvaries in degree according to the amount of undercooling. Many methodsfor treating hypothermia are already known. Generally, these compriseintroducing heat into the core of the body by some means to raise thebody temperature. Simple treatments can take the form of a warm drink.Sometimes warm air is blown around the body via air blankets. Such asystem is already well established in hospitals and marketed under thename Bair Hugger®. The system relies on heating up the periphery of thebody and using the patient's blood flow to draw the heat into the coreof the body.

One of the first physiological responses of hypothermia is peripheralvasoconstriction which reduces the amount of blood at the periphery ofthe body. This can make it difficult to introduce heat into the bodythrough the application of heat to the body surface. It is known thatvessels, including capillaries, arterioles, arteries, venoles and veins,can be made to vasodilate under conditions of negative pressure.Vasodilated skin regions, particularly on the forearm, can makeefficient heat transfer surfaces.

One system that applies negative pressure to a limb to reduce peripheralvasoconstriction whilst warming the periphery of. the patient to treatthe hypothermia is taught in U.S. Pat. No. 5,683,438 and sold under themark Thermostat® by Aquarius Medical Corp. In that system, a limb of thepatient is placed in a sealed chamber and. the pressure inside thatchamber is reduced to a negative pressure of between −20 to −80 mmHg(−2.7 to −10.7 kPa). At the same time, thermal energy is delivered tothe surface the limb using a thermal blanket, heat lamp or chemicalheating elements. Further developments to this system are described inWO-A-01/80790.

SUMMARY OF THE INVENTION

The device of the present invention generally utilizes a liquid to applya pulsating pressure to a local region of the body, thereby increasingthe blood flow in a local region of the body. This can be beneficial inproviding therapeutic treatments to a patient that may be suffering fromconditions or complications caused by, but not limited to, hypothermia,hyperthermia, stroke, heart attack, other ischemic diseases,neurosurgery, cancer and ulcers. Additionally, the devices of thepresent invention may provide therapeutic benefits by increasing thedistribution of contrast fluid to a local part of the body, increasingvenous circulation, increasing lymphatic circulation, changing thepharmacological distribution of drugs systemically and locally becauseof locally changed blood flow and possibly diffusion, promoting healingof tissues by increased blood flow, increasing antigen-antibody contactthrough increased blood flow, lymphatic flow and diffusion, increasingthe flow of substances between vessels and cells through increaseddiffusion.

In various embodiments of the present invention the device takes theform of a pressure chamber in to which a limb of the body can be placedto seal it from external conditions. The pressure chamber normally hasinternal walls which define, at least in part, a vessel for holding aliquid, whereby in use the limb can be immersed in a liquid contained inthe pressure chamber. The liquid surrounds and is in contact with thelimb with an air gap being present above the liquid in an upper regionof the vessel. The device further includes an element which is incommunication with the upper region of the vessel for varying thepressure above the liquid so as to generate pulses of pressure withinthe chamber. The pulses of pressure generated by the change in pressureabove the liquid are transmitted to the limb directly via the liquid.

The foregoing and additional advantages and characterizing features ofthe present invention and the methods of using the devices of thepresent invention will become increasingly apparent to those of ordinaryskill in the art by references to the following detailed description andto the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an example of a preferred apparatus for applying apulsating pressure to a limb;

FIGS. 2 a to 2 e illustrate various pressure curves that might be usedaccording to the state of the body;

FIG. 3 shows a plot of blood velocity in the brachial artery againsttime illustrating the change in blood velocity as the pulsating pressureis switched on and off;

FIG. 4 illustrates the effect pulses of pressure have on blood velocityfor pulses that are approximately 10 seconds (negative pressure)followed by releasing and 7 seconds without pressure (normalizing);

FIG. 5 illustrates a preferred embodiment of the apparatus in moredetail;

FIGS. 6 a-6 d illustrate further aspects in detail of the pressureapplication device used in the apparatus of FIG. 5;

FIGS. 7 a-7 c show how the pressure application device is able tooperate at different angles;

FIGS. 8 a-8 d show a preferred pressure application device for use on alower leg and foot being fitted to a patient;

FIG. 9 illustrates an example of a further device which incorporates abarrier layer between the liquid and the patient's skin;

FIG. 10 shows a comparison between the influence the preferred device ofthe present invention can have on the core body temperature compared toa conventional device during surgery of a patient;

FIG. 11 shows a comparison of the blood velocities of an arm subjectedto pulsating pressure and a control arm;

FIG. 12 shows a comparison of blood velocities of an arm subjected tonormal, constant and pulsating pressure and a control arm; and

FIG. 13 shows the change in tympanic temperature of a patient over timeduring treatment for hyperthermia.

DETAILED DESCRIPTION OF THE INVENTION

The devices of the present invention, in broad terms, are generallyapparatuses for applying a pulsating pressure to a local region of thebody. Various embodiments of these devices take the form of a pressurechamber in to which a limb of the body can be placed to seal it fromexternal conditions. The pressure chamber of these embodiments generallyhave internal walls which define, at least in part, a vessel for holdinga liquid, whereby in use the limb can be immersed in a liquid containedin the pressure chamber such that the liquid surrounds and is in contactwith the limb with an air gap being present above the liquid in an upperregion of the vessel, wherein an element is provided in communicationwith the upper region of the vessel for varying the pressure above theliquid so as to generate pulses of pressure within the chamber, andwherein the pulses of pressure are transmitted to the limb via theliquid. In other words these devices are characterized in that thepressure chamber does not contain additional means (e.g., a waterperfused mat) to separate the liquid from the surface of the limb. Thusa more simplified construction is possible than that used in the devicesof the prior art, thereby reducing manufacturing costs. The vessel wallsare preferably the internal walls of the pressure chamber, i.e., theprovision of additional liquid containment surfaces or chambers isavoided, keeping the construction of the device simple.

In one embodiment of the present invention, a pulsating negativepressure is generated in the chamber and preferably the pulse frequencyis less than the heart beat of the subject. By making the period of thepulses longer than the pulse of the heart, it has been found thatcirculation can be, improved through the influence of the appliedrhythmical pressure. In general the pulses should be longer than onesecond, preferably of the order of five or more seconds, but preferablyless than twenty seconds. It is noted that the period of the pulses canalso be varied. In effect the pulsating pressure drives the blood flowin a similar manner to a pump. This may generally be caused by theaction of the veins and arteries dilating and constricting at differentrates under the application of the varying pressure. A drop in pressurecauses local venous pooling of blood which is then forced through thenetwork of veins as the pressure increases, thereby improving localcirculation: Thus the present invention provides a device for increasingblood flow in a local region of a body through the application of apulsating pressure to an area of skin. Other health benefits may alsoresult.

Through the direct contact of the liquid, which is preferably water,there is a good transfer of the pressure pulses to the skin. Theinvention provides a device that is simple and easy to construct and yetprovides improvements over the known devices discussed above in terms ofthe improved local blood flow that is achievable. The use of liquids,such as water, as a transmitter of the pressure pulses means that theliquid can be in direct contact with the skin without posing unduehealth risks.

The present invention also extends to a method of operating such adevice and to a method of applying a pulsating pressure to a localregion of the body, in particular a method of increasing blood flow in alocal region of a body, through providing a device as described abovehaving a pressure chamber, introducing a limb into the pressure chambersuch that it is sealed from external conditions, filling or partiallyfilling the pressure chamber with a liquid to immerse the limb in theliquid so that it is substantially surrounded by and in contact with theliquid, generating a pulsating pressure within the chamber andtransmitting the pulses of pressure to the limb via the liquid. Themethod has application in medical and non-medical situations.

In many embodiments of the present invention, the liquid is circulatedin the device and around the surface of the limb (i.e., in directcontact with the skin). In this way the temperature of the liquid can beadjusted to influence the temperature of the blood in the surface layersof the limb. Circulating the liquid allows the temperature to becontrolled accurately.

In accordance with various embodiments, the device of the presentinvention is in the form of a pressure chamber in which a flow of liquidcan be generated. The chamber has an opening for introducing a limb intothe chamber for immersing it within the flow of liquid provided in thechamber. In this way the liquid is circulated within the chamber incontact with the surface of the limb. The device is provided with anelement or means to generate simultaneously pulses of pressure withinthe chamber and thereby exert a pulsating pressure on the surface of thelimb whilst the limb is immersed in the flow of liquid. In the methoddescribed above, the method would also include the step of circulatingthe liquid within the chamber and around the surface of the limbimmersed in the liquid.

More particularly, in various embodiments of the present invention, thepulsating pressure application devices include a housing defining apressure chamber having walls and an opening for receiving a limb. Aseal is provided for sealing the chamber from external conditions, theseal being arranged around the opening for sealing engagement with thelimb. A connection may be provided through a wall of the chamber tocommunicate the chamber with a pressure source that is at a pressuredifferent from atmospheric pressure for regulating the pressure withinthe chamber. An inlet and outlet may be provided in the housing forintroducing and discharging a liquid into and out of the chamber.Preferably the inlet and outlet are in communication with each other viaa fluid path that is defined by the internal walls of the chamber andthe surface of the limb once it has been introduced into the chamber,such that in use liquid flows from the inlet into the chamber,circulates around and in contact with the surface of the limb and isthen discharged via the outlet.

In various embodiments of the present invention, the liquid that is incontact with the skin is at a temperature different to that of the corebody temperature. Hence, the liquid is a thermal transfer medium thattransfers heat into or out of the body depending on whether it is at atemperature hotter or cooler than the core body temperaturerespectively. The temperature of the heat transfer medium and the rateof heat transfer may be sufficient to maintain the core body temperatureat a particular temperature, e.g., normal body temperature, or within adegree or two either side of the particular temperature. The temperatureof the heat transfer medium and the rate of heat transfer may also begreater so as to effect a change in the core body temperature of thesubject, e.g., a patient.

Thus there is also provided a method and apparatus for regulating thecore body temperature comprising the simultaneous application of athermal energy transfer medium and a pulsating pressure to a portion ofskin on a body, wherein the thermal energy transfer medium is a liquidand the liquid is in direct contact with the skin. The pulsatingpressure is applied to the skin by a device described above inaccordance with the present invention. Core body temperature regulationmay be useful in non-medical as well as medical applications.

Numerous advantages are achieved through this device. The constructionis far simpler than for known devices that aim to regulate the core bodytemperature. There is better thermal energy transfer from the liquid tothe surface of the limb because it is in direct contact and becausethere is greater heat transfer surface area. The device is easier to fitthan the known devices because, for example, there is no thermal blanketwithin the pressure chamber. The device can also be used on an arm or aleg without the need for different shapes and sizes of thermal blanket.The device of the present invention is therefore far more accommodatingfor use on different limbs and size of limb than the known arrangements.A single device can be used for different applications reducingequipment costs and storage issues.

The present invention provides therapeutic benefits in a number ofdifferent manners and/or applications. For example, the devices of thepresent invention can be utilized to enhance and maximize thermal energytransfer to or from the patient's limb. The direct contact of the limbwith the liquid increases the rate of energy transfer to or from theliquid to the limb. Generally, the rates of thermal energy transfer areproportional to the surface area in which transfer takes place. Byimmersing the entire limb in the liquid, the surface area in which heattransfer takes place is maximized.

The circulation of the liquid around the surfaces of the limb alsoimproves the thermal energy transfer between the liquid and the limb.First, the circulation allows for precise temperature control. Theliquid being introduced into the chamber and circulated can bemaintained at a precise temperature.

The circulation also allows for forced convection to take place. Forcedconvection allows for better energy transfer as compared to methodsusing conduction (e.g., placing a limb in contact with a heated watermattress) or using natural convection (e.g., immersing a limb in a stillbody of heated water). Conduction takes place when energy is transferredto or from one still material in direct contact with another stillmaterial. For example, if a limb were placed in direct contact with aheated water mattress, heat would be transferred from the water mattressto the limb. Natural convection takes place when energy is masstransferred to or from one large mass to a surrounding ambient medium(such as air or water). For example, if a limb were immersed in a bodyof still heated water, heat would be transferred from the body of waterto the limb. Forced convection takes place when energy is transferred toor from one large mass to a surrounding moving medium (such as air orwater). Forced convection is used in the present invention when a limbis placed in a body of heated water that is circulating around thesurfaces of the limb. Forced convection allows for maximum heat transferin comparison to prior methods using conduction or natural convection.

Likewise, a liquid medium allows for better thermal energy transfer thanan air medium. Mediums having a higher thermal conductivity and specificheat allow for better heat transfer than other mediums. The thermalconductivity and the specific heat of water are approximately 100-200times greater than in air. Thus, the present invention transfers energymuch better than forced air and other methods. Thus, by circulating aliquid rather than air, energy transfer is maximized.

The devices of the present invention also increase local blood velocityby application of pulsating negative pressure to the limb. Pulsatingnegative pressure increases the blood velocity in the limb much betterthan constant, negative alone. The increase in blood velocity isadvantageous because the blood warmed in the limb can be quicklytransferred from the limb to the remaining body.

The thermal energy transfer medium in various embodiments of the presentinvention is a liquid and is preferably water since it is cheap,non-toxic and has a high specific heat capacity. In use the water maycause wrinkling of the skin, but the benefits of the system far outweighthis slight disadvantage. The wrinkling disappears minutes after thewater is removed. Some patients reported improvement of their skincondition after being treated with the device. None reported negativeeffects.

The water can include additives to minimise this effect and to reducethe discomfort to the patient, e.g., painkillers or local anaestheticagent. Additives may be chosen to reduce shivering or to encouragevasodilation in the blood vessels. These could be given systemically orlocally, and could be administered before or simultaneously with theinvention, for example, intravenously, intra-artery, oral, rectal, etc.In the most preferred embodiments, painkillers or local or regionalanaesthetics are administered prior to the limb being inserted into thechamber.

Viewed from another aspect, in broad terms the present inventionprovides a method of transferring thermal energy to or from a bodycomprising introducing a limb of a patient into a flow of liquid whichis at a temperature different to that of the core body temperature ofthe patient whilst simultaneously applying a pulsating pressure to thesurface of the limb being exposed to the flow of liquid.

Thus, in one embodiment, the present invention provides a method oftransferring thermal energy to or from a body. The method of thermalenergy transfer generally includes providing the device of the presentinvention for applying pulsating pressure to a limb. As previouslysuggested, an embodiment of such a device includes a chamber having aseal, a connection communicating the chamber to a pressure source thatis at a pressure different from atmospheric pressure, and a liquid inletand outlet. Next, a limb is introduced into the chamber and the sealseals against the limb to provide an enclosed environment. Once the limbis sealed in the chamber, a liquid is introduced into the chamber viathe inlet and later discharged via the outlet. The liquid follows afluid path defined by the walls of the chamber and the surface of thelimb such that the liquid is circulated around, comes in contact withthe surface of the limb and simultaneously generates pulses of pressurewithin the chamber.

The present invention also provides a method of applying a pulsatingnegative pressure to a local region of the body to provide therapeutictreatments. These treatments can be administered to a subject by firstproviding a pressure chamber. Next a limb may be introduced into thepressure chamber such that the limb is sealed from external conditions.Once the limb is sealed in the chamber, a liquid may be introduced intothe pressure chamber so that the limb is substantially surrounded by andin direct contact with the liquid. Finally, negative pressure isalternately generated and released within the chamber, therebytransmitting to the limb the negative pressure through direct contactwith the liquid.

The alternately generated and released negative pressure normallycomprises alternately generating negative pressure for a predeterminedtime interval and releasing the negative pressure for a predeterminedtime interval. For example, the alternately generating and releasingnegative pressure within the chamber comprises alternately generatingnegative pressure for a time interval of between about 1 and 20 seconds,preferably about 5 and 15 seconds, and releasing the negative pressurefor a time interval of between about 2 and 15 seconds, preferably about5 and 10 seconds. In particularly preferred embodiments, the alternatelygenerating and releasing negative pressure within the chamber comprisesalternately generating negative pressure for a time interval of about 10seconds and releasing the negative pressure for a time interval of about7 seconds.

Likewise, the alternately generating and releasing negative pressurewithin the chamber preferably comprises alternately generating anegative pressure between about −10 mmHg and −120 mmHg, preferably −20mmHg and −80 mmHg, and releasing the negative pressure. For example, inpreferred embodiments, the alternately generating and releasing pulsesof negative pressure within the chamber comprises alternately generatinga negative pressure of about −40 mmHg and releasing the negativepressure.

The liquid introduced into the pressure chamber of the devices of thepresent invention generally comprises one or more liquids having atemperature different than the core body temperature. For example, waterhaving a temperature different than the core body temperature may beutilized in the device of the present invention. In certain embodiments,the method further comprises circulating the liquid around the surfacesof the limb to transfer heat to or from the limb. The method may alsofurther comprise administering an anesthetic to the limb prior tointroducing the limb into the pressure chamber.

An additional method of the present invention also includes a method ofapplying a pulsating negative pressure to a local region of the body.This method also comprises providing a pressure chamber containing agas. Once the chamber containing a gas is provided, a limb may beintroduced into the pressure chamber such that the limb is sealed fromexternal conditions. Next, the pressure chamber is partially filled witha liquid so that the limb is substantially surrounded by and in directcontact with the liquid while leaving a gas pocket above the liquid inan upper region of the chamber. The gas pocket is then continuouslysupplied a constant negative pressure followed by the introduction of apositive pressure into the gas pocket at predetermined time intervals totemporarily release the negative pressure within the chamber.

The present invention further provides a method of transferring thermalenergy to and from a body. For example thermal energy is transferred toand from the body by first providing an enclosure. Next a limb isintroduced into the enclosure such that the limb is sealed from externalconditions. Once the limb is sealed from external conditions in thechamber a thermal exchange liquid is placed into the chamber so that thelimb is completely surrounded by and in direct contact with the liquid.The introduced thermal exchange liquid will generally have apredetermined temperature different than the core body temperature.Next, the introduced thermal exchange liquid is circulated around thesurfaces of the limb, the liquid thereby transmitting heat to or fromthe limb. A pulsating negative pressure is then generated within theenclosure, thereby transmitting the pulsating negative pressure to thelimb through direct contact with the liquid. Finally, the circulatedthermal exchange liquid may be discharged from the enclosure.

Additionally, the devices of the present invention further provides amethod of treating hypothermia in a patient's body. The method oftreating hypothermia generally comprises introducing a limb into apressure chamber such that the limb is sealed from external conditions.Once the limb is sealed in the pressure chamber a thermal exchangeliquid is introduced into the pressure chamber to immerse the limb inthe liquid so that the limb is substantially surrounded by and incontact with the liquid. The thermal exchange liquid normally has atemperature warmer than the core body temperature so that the heat inthe liquid is transmitted to the limb. Next, negative pressure isalternately generated between about −10 mmHg and −120 mmHg, preferablyabout −20 mmHg and −80 mmHg, within the chamber for a time interval ofbetween about 1 and 20 seconds, preferably about 5 and 15 seconds, andreleasing the negative pressure for a time interval of between about 2and 15, preferably about 5 and 10 seconds.

The effects of the pulsating pressure, at least in one preferredembodiment, are believed to be as follows. Firstly a negative pressureis generated leading to an increase in transmurale pressure. This leadsto a mechanical local dilatation of the vessels because of the drop inpressure. The veins are then dilated more than the arteries due to thegreater elastic nature of the walls. Within a few seconds the negativepressure leads to a local venous pooling of blood. During this periodthe blood flow also increases in the arteries due to dilatation. Thepooling of blood is believed to be present in all layers (plexus) fromthe subcutaneous to the more central veins. The pooling of blood in theveins brings more blood closer to the surface of the skin, and therebymakes it more accessible to heat transfer (gain/loss). Returning theblood through more peripheral veins reduces the heat exchange betweensupplying arteries and returning veins, the counter current effect. Whenthe pressure drops back to zero (relative to atmospheric pressure), theveins constrict and the blood is forced towards the direction with thelowest resistance to flow. The venous valves will effectively force theblood in the direction towards the heart only. If a positive pressure isadded the transmurale pressure will drop. The intramural pressure ismuch larger in the arteries. This leads to a relative largerconstriction of veins compared to arteries, and the veins are “emptied”of blood. The veins are now ready to receive more blood, and thepressure starts to drop again. The microvasculature capillaries alsoappear to be affected and there is also a possibility that the lymphaticsystem is affected too, and that lymph flow is increased. Lymphaticcirculation is believed to be affected by the pulsating pressure in thesame way as the veins because the vessels also have one-way valves. Asthe vessel walls are even thinner than in the veins, a system operatingon the lymphatic system alone may be utilised by operating at lowerpressures (including positive pressures) but following the samepulsating mode, thereby minimizing the effects on the arteries/veins(because increased blood flow can have a negative effect on oedemaetc.). An example of this may be to apply pulses with 15 seconds on and15 seconds off at less than 20 mmHg (2.7 kPa).

Using an ultrasound Doppler measuring technique, it has been found thata preferred embodiment can improve blood velocity by up to at least 30%in the brachial artery. In experiments, an average of at least 50%increase in blood velocity and an increase of 200% in a single subjecthave been witnessed. By pulsating the pressure, it is believed tofacilitate the immediate and repeated increase of blood velocity withoutinducing a reflex constriction as a result of the venus pooling. This isan effect that appears to occur with the known constant negativepressure arrangements. The reflex is more pronounced in the legs,probably because it acts as a means of preventing pooling of blood whenstanding. Under constant negative pressures of −40 mm Hg (−5.3 kPa) itwas found that blood flow decreased by up to 20%. This is probably dueto the veino-arterial reflex that is elicited when the veins aredistended. Receptors in the walls of the veins sense the dilation, andthrough a spinal reflex arch the supplying arterioles are constricted.In the present invention, the pulsating of the pressure tends to preventthis, and the blood flow is instead increased. Without anypharmacological or other blocking agent, the invention has been found towork best on the arms because of the reduced reflex constriction effect.Where blocking or reducing of the reflex is possible in the legs, abetter circulation may be achieved than in the arms and there is also agreater total area of heat transfer to benefit from.

The increase in blood flow is dependent on the patient's thermal state.If the patient is cold, the vessels of the skin are constricted toeliminate heat loss. The subcutaneous adipose tissue is also aneffective insulator. In this way heat transfer (gain/loss) through theskin is limited. Under these conditions, the present invention can bevery effective. The vessels are “forced” to circulate blood and heatexchange with the heat transfer medium can be effectively restored.

In a warm state, the vessels are already dilated. In this situation thepotential to increase the flow may be reduced. However, the applicationof a positive pressure may help the veins to empty blood to the heart.If cold water is applied locally to cool down a warm patient, there is atendency for the blood vessels to constrict. A pulsating pressure willkeep the vessels open, and help with the effective transfer of heat awayfrom the body.

The locally applied heat affects the circulation locally. Cold water canconstrict vessels locally ands warm water can dilate vessels. This cansometimes work to the disadvantage of the patient. By applying apulsating pressure the circulation can be “forced” through, whilst theskin works as a thermal energy transfer surface, e.g., as a radiator.

The increased blood flow can be utilised in many different ways. Thepotential applications of the invention are numerous. The invention maybe used in connection with several important clinical problems listedbelow:

-   -   Prevention of hypothermia by heat transfer to the body (heat        gain)    -   Treatment of hypothermia by heat transfer to the body (heat        gain)    -   Prevention of hyperthermia by heat transfer from the body (heat        loss)    -   Treatment of hyperthermia by heat transfer from the body (heat        loss)    -   To induce hypothermia to treat stroke patients, heart attack and        other ischemic diseases, for neuro surgery etc.    -   To induce hyperthermia to treat cancer patients globally and        locally    -   Treatment of ulcers that has difficulties to grow by increasing        blood flow locally (leg ulcers)    -   Changing the pharmacological distribution of drugs systemically        and locally because of locally changed blood flow and possibly        diffusion    -   Increasing the distribution of contrast fluid to a local part of        the body    -   Increasing venous circulation    -   Increasing lymphatic circulation    -   Promoting healing of tissues by increased blood flow    -   Increasing antigen-antibody contact through increased blood        flow, lymphatic flow and diffusion    -   Increased flow of substances between vessels and cells through        increased diffusion.

The physiological effects on the body of negative pressure has been thesubject of research with the main conclusions that 90% of the negativepressure is distributed to the underlying tissue with increasedtransmurale pressure and dilatation of vessels and changes in venous andarterial circulation.

The reference to a “limb” used herein should be interpreted as being anypart of a human or animal body that can be easily introduced into thedevice, for example, an arm or leg or portion of an arm or leg, e.g.,forearm, hand, lower leg, foot, or possibly even more than one of suchparts of the body if the situation allows. In certain situations it maybe preferable to use, more than one device to increase the amount ofheat transfer. For transferring thermal energy to or from the patient,the greater the surface area of skin contact and the more efficient thatarea of skin is at transferring thermal energy from or to the patient'sblood, and hence the core of the patient, the better. For this reason,it is preferred to use the patient's forearm in the device. There isalso less reflex constriction in the forearm than the leg of a patient,leading to improved thermal energy transfer. Where maximum heat transferis required, the device should be large enough to accommodate the wholearm or at least as far up the upper arm as possible, e.g., the middle ofthe upper arm. The seal, e.g., a sealing cuff, preferably fits above theelbow around the patient's biceps and triceps with the rest of the armand hand extending into the device. Not only does this maximise thesurface area of skin exposed to the liquid but it also means that theblood will be flowing in the distended venous plexus in close proximityto the liquid for longer as it flows through the upper arm, forearm andhand. In this way therefore, the volume of blood and the rate of bloodflow are both maximised.

Where the device is being used to transfer only small amounts of thermalenergy, for example, warming of the body in preparation for a sportingactivity, cooling of a body on a hot day or warming on a cold day forcomfort, etc., a smaller thermal energy transfer area, such as just thehand or foot, may be sufficient. The device could take the form of amitten or boot, for example. Thus, for applications, say, where a lesserextent of heat transfer is required, the sealing cuff may seal closer tothe end of the limb or perhaps even a second seal may be provided forthe hand or foot to be external of the device once the arm or leg is inplace.

Access and heat transfer requirement will largely dictate where thedevice can be applied on the body. If an operation is being perforatedon the top part of the body, then it may be preferable to use the deviceon the patient's leg so that the device is out of the way of thesurgeon. However, in order for the device to work effectively,particularly in the treatment and prevention of hypothermia, it must beable to transfer heat to or from the patient at a rate which is fasterthan the patient can lose or generate heat through normal biologicalprocesses. From preliminary studies, it has been found that this cannotalways be achieved in a healthy normal person using a device enclosingjust the lower leg and foot although some benefit may be achieved incertain situations. In theory it is also conceivable that a device of anappropriate size and having an appropriate seal could receive two legsof a patient to maximise thermal energy transfer.

In use, a pocket of air remains above the surface of the liquid in thechamber. Pressure within the chamber is varied by altering the pressureof the air in this air pocket. The pressure and the changes in thepressure within the chamber are transferred to the surface of the limbvia the liquid.

The reference to “air” used herein as a pressure regulating medium is inno way intended to limit the invention to devices that just use air.Other gases, for example, inert gases, would also be suitable althoughwould add considerably to the costs of operating the device.

Preferably the gas is air and the pressure source is a vacuum line,which are commonplace in hospitals. Where only compressed air isavailable, a converter can be used to convert this to a source ofnegative pressure. Such pressure sources are at substantially constantpressure and therefore a regulating device needs to be provided togenerate a pulsating pressure. A pump could provide the pulses ofpressure directly or could be used in conjunction with a regulatingdevice to generate the pressure pulses. Where the device is being usedin a non-hospital environment, for example, as part of rescue equipment,then it may be necessary to use a pump, which may have its own powersource or be operated manually. Circulation of the liquid could beachieved via a stirrer located in the chamber.

Preferably the pressure source is at a pressure below atmosphericpressure, thereby causing a drop in the pressure within the chamber toapply a negative pressure (i.e., the amount of pressure belowatmospheric pressure) to the limb. The chamber should be configured towithstand negative pressures of at least −80 mmHg (−10.7 kPa),preferably considerably more. That is to say that a negative pressure of−80 mmHg (−10.7 kPa) within the chamber would correspond with aninternal pressure of 680 mmHg (90.7 kPa) based on the standard value foratmospheric pressure of 760 mmHg (101.3 kPa).

Preferably the pressure source is at a negative pressure of −80 mmHg(−10.7 kPa), more preferably −60 mm Hg (−8.0 kPa) or less and mostpreferably is at around −40 mmHg (−5.3 kPa) in order to reduce thepossible complications that are thought to arise from the application ofhigher negative pressures. The purpose of the negative pressure is toencourage local vasodilation in the surface of the limb, so the negativepressure should be chosen to maximise this whilst minimising the risk ofpossible complications. Pulsating the negative pressure has been foundto encourage blood flow and for this reason a pulsating negativepressure of 0 to −40 mmHg (0 to −5.3 kPa) is preferably generated in thechamber.

Preferably the pressure source is at a constant pressure, preferably aconstant negative pressure, and air is bled into the chamber via a valveto return the pressure within the chamber to or towards atmosphericpressure. Because of the time for which the valve is open or the rate atwhich air can enter through the valve, the chamber may not be returnedcompletely to atmospheric pressure between the pulses of pressure and asmall amount of negative pressure may remain each time in the chamber atthe end of the pulse. This might be, say, between 0 and −20 mmHg (0 and−2.7 kPa) or more preferably between 0 and −10 mmHg (0 and −1.3 kPa),and more preferably still between 0 and −5 mmHg (0 and −0.67 kPa). Mostpreferably, the rate at which air can enter through the valve and thepulse period are such that the pressure within the chamber is returnedto atmospheric pressure during each pressure pulse. In the mostpreferred embodiments, the change in the chamber pressure issubstantially instantaneous such that the time taken to change thepressure takes only a small fraction of the time for which the valve isopen, for example, less than 50%, preferably less than 25% and mostpreferably less than 10% of the time that the valve is open during apressure pulse. It is preferred that the plot of pressure against timefollows a substantially square toothed plot with sharp transitions atthe pressure changes. In practice, some rounding of the transitions mayoccur. Similarly, the pressure source should have sufficient capacity tobring the pressure to the desired negative or positive pressure asquickly as possible and preferably within similar working levels as thatfor the valve.

For certain applications, it may be preferred to vary the pressurebetween atmospheric pressure, or substantially atmospheric pressure, anda positive pressure of corresponding magnitude to those values givenabove for negative pressure. In other applications, oscillating thepressure between positive and negative pressures may be beneficial. Forexample the pressure may be pulsed between −40 mmHg (−5.3 kPa) and +15mmHg (+2 kPa) with time sequences of 7 seconds drop in pressure to −40mmHg (−5.3 kPa), 7 seconds rise in pressure up to 0 mmHg (0 kPa) andcontinuation of increased pressure through to +15 mmHg (+2 kPa) over thenext 5 seconds followed by a drop to 0 mmHg (0 kPa) over the following 2seconds with the sequence repeated and the pressure dropping to −40 mmHg(−5.3 kPa) over the next 7 seconds.

In a number of earlier known systems in which an oscillating pressurewas applied to a patient, it was thought best to vary pressure in timewith the heart beat. The present inventors have found that a longerperiod to the oscillation is better. That is to say that each step ofnegative pressure application should last more than one second,preferably more than three seconds, more preferably five seconds orlonger, most preferably about seven seconds or longer. However there isan optimum since longer pulses greater than 30 seconds and constantpressures tend to reduce blood flow. Relaxation of the pressure toatmospheric pressure should be for corresponding periods, although maybe of slightly different duration.

Preferably the times for which the valve is open and shut are not equal,and hence the pulses of negative/positive pressure and atmosphericpressure are not equal. Preferably the length of the negative/positivepressure pulse is longer than the period “at rest” when the pressure isat atmospheric pressure or returning to atmospheric pressure.

Preferably it is 5% longer or greater, more preferably greater than 10%longer and most preferably more than 25% longer. In one embodiment thathas been found to work particularly well, negative pressure was built upfor 7 seconds and released for 10 seconds.

The valve could be positioned in the communication path to the pressuresource, but is preferably provided in the chamber housing, andpositioned near the top of the chamber when it is in use so that air isbled into the air pocket rather than the liquid. Under negative pressureconditions, if the valve were positioned below the level of the liquid,it would create bubbles in the liquid and may affect the temperature ofthe liquid. Under positive pressure conditions, submerging the valvecould result in liquid being ejected from the chamber. A microprocessorcan be programmed to operate the valve and different settings could bestored for different applications.

The housing could be any shape, for example, rectangular, i.e.,box-shaped, but is preferably tubular and of circular or ovalcross-section, i.e., generally cylindrical. A rounded surface is moreable to withstand negative pressures and allows the housing to be rockedslightly from side to side to alleviate discomfort to the patient. Theseal may restrict movement of the limb with respect to the chamber sosmall amounts of rotation of the limb can be taken up through rollingthe housing slightly. This would not be possible with a housing oftriangular or square cross section having flat sides, where a moreflexible sealing system or rocking surfaces may be required in certaincases. If the device is intended specifically for the lower leg and footof a patient, then it may comprise two sections; one tubular section tohouse the patient's leg and a box section at the end that is of largerdimension to accommodate the patient's foot. The tubular section mayallow the device to be rocked from side to side whilst the flat-sidedbox section hangs off to one side of the operating table. The importantadvantage is that the shape of the chamber is not critical to theoperation of the device, other than it must be of a size sufficient toaccommodate the limb of the patient. As a result it can be made muchmore cheaply than existing devices yet benefits of improved thermalenergy transfer to the patient can be achieved.

In embodiments where the housing comprises an elongate cylinder ofcircular cross-section having a curved side wall and a flat end wail,preferably the connection to the pressure source is provided in thecurved side wail of the housing for positioning as a highest point inuse. In this way, the likelihood of liquid being sucked out of thechamber by the negative pressure source is reduced. More preferably twoconnections are provided in the side wall of the housing, one proximatethe end wall of the housing and other proximate the seal and opening atthe other end of the housing. As it may be difficult to position apatient so that the limb is exactly horizontal, one end of the housingmay be raised slightly higher than the other. Providing two connectionsin the housing that are connected to the pressure source by a common airline fitted with a Y-connector, ensures that at least one of theconnectors is in communication with the pocket of air above the surfaceof the liquid. Preferably the Y-connector is positioned at a heightabove the surface of the liquid so that the liquid tends not to becomedrawn up one of the air lines if one of the connections becomessubmerged, for example, when repositioning the limb of the patient.Under negative pressures of −40 mmHg (−5.3 kPa), a height of 50 mm ormore is preferred for this. Alternatively, a valve could be positionedto select one or other or both of the connectors for connection to thepressure source.

The seal may be in any form which is capable of sealing the gap betweenthe opening of the chamber and the portion of the limb, for example, arubber cuff or the like. Under negative pressure condition, atmosphericpressure can assist the sealing engagement of the seal with the limb.Soft materials such as neoprene O-rings are preferred. A seal may befitted around the limb prior to insertion in the chamber and thenconnected to the chamber to seal it off once the limb is positionedinside. One of the preferred uses of the device is for treatinghypothermia where it is important to circulate the warmed blood from theperipheral region of the limb around the body and through to the core.Too tight a seal can act. as a tourniquet and restrict this circulation.Where the device is to be used to apply positive pressures, additionalmeans may be required to prevent escape of air. In one arrangement, theair line is fitted around the seal, so that increases in the positivepressure causes greater pressure to be applied to the seal in step whenthe chamber is at a higher internal pressure, In another embodiment aninflatable cuff, preferably of latex or the like, is used.

A preferred arrangement for alternating positive-negative pressures hasbeen found where the seal, preferably made from rubber/silicone etc., isT-shaped and provided with two “wings” in the form of flaps that extendfrom a central sealing member into sealing engagement with the limb. Oneflap or “wing” extends inside the chamber and is pushed towards the skinsurface by the positive pressure, whereas the flap or “wing” outside thechamber will be sucked towards the skin during the negative pressureperiod.

The seal is also important because it creates a region of relativelyischemic tissue in the skin beneath the seal during negative pressure.When the pressure is released vasoactive substances (potassium, ADP,adenosine etc.) travel with the blood and dilates the arteries below toincrease blood flow.

The liquid in the chamber is for transferring thermal energy to or fromthe limb. As mentioned above, preferably this liquid is water. Fortreating hypothermia, warm water at between 40 to 45° C., preferably 43°C. is used. Some patients will feel pain at temperatures greater than43.5° C. For treating hyperthermia, cooler or cold water at temperaturesof below 35° C., or more preferably 30° C. or below, is used. Waterbelow 15° C. can cause the nerve “pain” fibres to start firing.

In situations wherein the temperature of the heat transfer medium or theamount of heat transfer surface available is not sufficient to effect achange in core body temperature fast enough, a regional anaesthetic maybe administered to the limb, thereby blocking signals fromthermoreceptors so as to decrease sympathetic activity to the vesselspreventing vasoconstriction. By preventing shivering with a fullsurgical anaesthetic to the arm, say, with pethidin when trying toinduce hypothermia, heat transfer from the body core can be improved.The combination of a regional anaesthesia with cooling, whilst being apreferred feature of the invention described above, is believed to benew in its own right.

Thus a second embodiment of the invention disclosed herein provides asystem for effecting a change in the core body temperature of a patientcomprising the simultaneous transfer of thermal energy from a limbwhilst subjecting the limb to a pulsating pressure, preferably apulsating negative pressure, wherein an anaesthetic agent isadministered to the patient prior to the transfer of thermal energy toreduce sympathetic responses in the limb of the patient. The secondembodiment can be used in conjunction with the apparatus for the otherembodiments disclosed herein.

Thus in the above methods described with reference to the firstembodiment of the invention, preferably the step of providing a regionalanaesthesia to the limb, for example, by administering an anaestheticagent to the patient, is included.

In a preferred arrangement, a regional anaesthesia is given in thebrachial plexus prior to applying the method of the present invention tothe arm of the patient. The regional anaesthetic has the following maineffects:

-   -   Blocks sympathetic activity to the blood vessels, thereby        dilating the vessels in the arm (efferent signals). This is        important to the efficient operation of the method.    -   Blocks afferent nerve signals from all receptors in the arm to        the central nervous system. They have effects on the temperature        regulating centre reducing signals which tell the body to start        heating/shivering/constriction.    -   Relieves the patient of pain, which again can be important for        blood pressure control.

By anaesthetising the limb, e.g., the patient's arm, prior to itsinsertion in the devices described above, liquids at higher or lowertemperatures than those suggested previously, i.e. greater than 43.5°C., more preferably greater than 45° C., or less than 30° C., morepreferably 10° C. or below, could be used to provide a greater thermalenergy transfer across the skin of the patient.

At temperatures less than 25° C., and preferably less than 23° C. wherethere is a temperature gradient of at least 14° C., regional anaesthesiais particularly beneficial because of the amount of control that thisgives over the core body temperature of the patient, e.g., maintainingor lowering the core body temperature. Additionally, chilled fluids maybe administered to the patient (e.g., at 4° C.) to lower the bodytemperature by a few (2-3) degrees, prior to maintaining the low corebody temperature by operating the device at 23° C. Both the induction ofhypothermia (e.g., for stroke treatment) and treating hyperthermia couldbe done this way.

This second embodiment of the present invention also has applicationwith some of the prior art devices and may provide a solution to thepoor heat transfer rates that are currently achievable with thosedevices.

Additionally, situations may occur wherein wrinkling of the skin iscaused by long exposure of the skin to liquid when the limb is placed ina device of the present invention. However substances may be added tothe liquid to minimize this and alleviate any discomfort caused. Forexample softeners and moisturizers know in the art may be added to theliquid to reduce the wrinkling of the skin. Another solution is to use awater perfused mat that is arranged to provide simultaneously pulses ofpressure to the limb where it is in contact with the mat whilsttransferring thermal energy. These systems are known from the prior art.However, an ordinary heating blanket (water perfused) will have too muchair and areas of non-contact to be effective enough to regulate bodytemperature reliably.

A solution to this problem is to utilise “double” suction, in which thenegative pressure is divided into an “internal” and an “external”negative pressure. The internal pressure, being only a few mmHg, e.g.,less <−5 mmHg (<−0.67 kPa), is applied between the skin and thewater-perfused part of the device (e.g. a blanket). This will suck thematerial towards the skin, and maximize the contact between the watercompartment and the skin. The internal pressure may be constant, pulsedor administered only at initial administration of the pressure to ensureadequate contact of the mat or water blanket to the limb, therebyoptimising the heat transfer effect. Thin material, elastic ornon-elastic with relatively high thermal conductance, for example,silicon, latex etc. Then the external pulsating pressure (e.g., pulsesof negative pressure) is applied outside the water blanket. This doublepressure is believed to be critical to optimise the heat transfereffect. Thus this system would provide a way of transferring thermalenergy to or from a subject, whilst simultaneously providing a pulsatingpressure, in applications where direct contact with water is not wanted.The device could take the form of that used in the first embodiment ofthe invention except that instead of the limb being immersed in a liquidcontained within the chamber, the limb is instead surrounded by liquidcontained within the chamber but separated from that liquid by a layerof flexible material.

Thus, in a third embodiment of the invention disclosed herein, there isprovided a device for applying a pulsating pressure to an area of skinon a limb of a body comprising a pressure chamber into which the limbcan be inserted, a barrier layer of flexible material housed within thatchamber for engagement against the skin, the barrier layer defining aninner region within the pressure chamber for receiving the limb which isseparated from a flow of liquid within the chamber, wherein the deviceincludes an element or means for generating a pulsating pressure withinthe pressure chamber, and an element or means for generating a negativepressure between the barrier layer and the area of skin to maintain thebarrier layer in contact with the area of skin. Preferably the barrierlayer takes the form of a sleeve extending along the middle of thedevice, e.g., along a central axis of a cylindrical pressure chamber.This ensures contact over a greater surface area of the limb than priorart devices which may contact less than 50% of the limb, e.g., bycontacting just one side of an arm. The flow of liquid may be partiallycontained by the walls of the pressure chamber acting as a containmentvessel or contained within a water perfused mat.

With this embodiment, the most important feature is to keep the regionbetween the skin and the water barrier layer substantially free from air(vacuum). This helps to ensure that the thin material containing thewater will stick on to the skin even if there is an external pulsatingpressure being applied. The “vacuum” in this region (e.g., 1-3 mmHg) maybe constant instead of pulsating together with the external pressure.Sweat from the skin of the patient will accumulate in this regionbetween the skin and the barrier layer which will assist in the heatconduction.

This invention also provides a method of applying a pulsating pressureto an area of skin on a limb of a body using the above describedapparatus for the benefits described in relation to the otherinventions. The method includes the steps of generating a negativepressure between the barrier layer and the area of skin, generating aflow of liquid within the pressure chamber adjacent the skin, generatingpulses of pressure within the chamber, preferably pulses of negativepressure, and transmitting the pulses of pressure to the skin throughthe barrier layer. Preferably the method includes transferring heat toor from the skin whilst simultaneously applying pressure pulses. Thussurrounding the limb with a heat transfer medium, either by immersing itin the medium or separating it from the medium by a thin flexiblemembrane which is drawn tight onto the skin via suction, provides acommon advantage of maximising the heat transfer area available, makingthe apparatus more effective at influencing the core body temperature.Furthermore, the reduction or prevention of a response in thesympathetic nervous system, at least locally in the limb through ananaesthetic agent, provides the advantage of maximising the heattransfer across the area available, again making the apparatus moreeffective at influencing the core body temperature.

Other possibilities for the device are also envisaged. For example, thedevice could have walls containing salts that, after being catalysed,can produce heat by an exothermic reaction. This could be of benefit inan acute situation where it is necessary to start heating quickly andperhaps where an external power source is not available. This heatingmeans may be in addition to the other heating sources, for example, tobe used as an emergency heat source.

Another possibility for emergency equipment is to have the entire devicemade of a lightweight inflatable material. Using a high pressure source,the device can be inflated so that the walls become stiff. The highpressure source (for example, a pressurised gas) can then be used topower the pulsating pressure for a period until external power can beprovided from elsewhere.

One further possibility is to provide different pressures and/ortemperatures in different compartments within the device so that, forexample, the patients' hand can be kept warm to make the blood followthe superficial veins when it returns to the core, but on its way backthe blood can then be cooled because it is more accessible. It is seenthat this could improve core cooling rates.

Certain preferred embodiments will now be described by way of exampleand with reference to the accompanying drawings, FIGS. 1-13.

FIG. 1 illustrates a system for applying a pulsating pressure to a localregion of the body. Shown fitted to the arm 1 of a patient 2 is a device3 comprising a pressure chamber 4 having an opening 5 at one end intowhich the arm 1 is inserted. A seal 6, fitted to the arm 1, seals thepressure chamber 4 from external conditions. The pressure chamber 4 isprovided with an inlet 7 and an outlet 8 for feeding a liquid 9, forexample, warm water, into and out of the pressure chamber 4. Connectors10, 11 may be fitted to the inlet 7 and outlet 8 respectively to connecteasily the flow of liquid. Valves (not shown) can be used in thesepositions to control the flow of liquid. As shown in FIG. 1, the arm 1is immersed in the liquid 9 but an air gap 12 exists above the liquid 9.In one embodiment the pressure chamber 4 is only three quarters filedwith liquid 9. The pressure in this air gap is pulsated to generatepulses of. pressure that are transmitted to the arm 1 of the patient 2via the liquid 9.

In the illustrated embodiment, the pressure chamber 4 is cylindrical inshape and a region of the circumferential wall 13 is provided with aconnection piece 14 in communication with a pressure source 15.Preferably two connection pieces 14 are used with connectors 16. Valvesmay be provided to isolate the connection pieces 14 as desired (forexample, in place of connectors 16). The pressure source 15 ispreferably a suction device to suck air out of the pressure chamber 4,i.e. to create a negative pressure in the pressure chamber 4.

In order to pulsate the pressure, air is bled back into the pressurechamber 4 from outside. An air inlet at connection 17 with a controllingvalve 18 can be provided to bleed air back into the air gap 12.Alternatively, and more preferably, air can be introduced into thepressure lines 19 linking the pressure source 15 to the device 3 throughconnection 14, for example, via a regulator 20. For both arrangements,connection 17 can also provide an inlet for filling the pressure chamber4 with water prior to starting the pump. A pressure recorder 21 with anoutput 22 is provided to monitor the pressure within the device 3. Theregulator 20 (for example comprising magnetic valves) and any additionalvalves provided can be controlled with a suitably programmed computer23.

FIGS. 2 a to 2 e illustrate five examples of pressure curves that couldbe generated within the device 3, according to the state of the body andthe condition being treated. In FIG. 2 a, pressure varies between 0 and−40 mmHg (0 and −5.3 kPa) for periods of 7 and 10 seconds respectively.In FIG. 2 b, the pulses last 5 seconds in a complete cycle time of about10 seconds. In FIG. 2 c the pulses are about 7 seconds in length. InFIG. 2 d, the pressure is oscillated between 0 and −40 mmHg (0 and −5.3kPa) for pulses of about 3 seconds each. In FIG. 2 e, the negativepressure pulse lasts about twice as long as the time at atmosphericpressure.

In FIG. 3, blood velocity (in essence, blood flow) in the brachialartery is shown with respect to time and how this varies under theinfluence of pulsating negative pressure and when the pulsating pressureis switched off. Blood velocity/flow was measured using ultrasoundDoppler and laser Doppler measuring techniques. Ultrasound Doppler,which measures blood velocity, is an important technique as measurementsare made outside the device. Making the reasonable assumption that theblood vessel diameter is constant, then the velocity will beproportional to flow (volume/time). The values were transferred to acomputer by an ECG recording, the velocities can be sampled beat bybeat. As shown in FIG. 3, the pulsating pressure leads to a significantincrease in the mean measured arterial blood velocity/flow.

FIG. 4 shows a detailed one minute recording. The negative pressure isbuilt up for 10 seconds and released for 7 seconds (upper panel). Theblood velocity in the brachial artery is measured outside the pressurechamber 4. The blood velocity increases to a certain point, about −25mmHg (−3.4 kPa), before it drops. This is thought to be due to a reflexconstriction of the arteries because of the venus pooling. Letting thepressure drop again, facilitates the immediate and repeated increase ofblood velocity without the reflex restricting the blood flow as canhappen with a constant negative pressure.

FIG. 5 illustrates another embodiment of the apparatus. The samereference numerals as used in FIG. 1 have been used in this embodimentwhere they correspond. The pressure chamber 4 comprises an acrylic tube.In a preferred embodiment, the tube had a diameter of 16 cm and a lengthof 50 cm. The seal 6 comprises a ring of carved POM 24 (diameter 16cm×10 cm) as an extension piece supporting an inner neoprene seal 25 andan outer rubber seal 26. Inlet 7 and outlet 8 are provided to feedliquid, for example, water, via feed lines 27. These connect to a waterbath 28 for controlling the temperature of the liquid and to a pump 29,for example, a peristaltic pump for circulating the liquid.

The feed lines 27 are preferably silicone except for where they extendthrough the water bath. In the water bath 28, copper pipes are used toensure good heat transfer. The copper pipes are preferably about 6 mlong, ensuring equilibrium of the water temperature between the waterbath and the water in the pipes. The water bath could heat the water to45° C. and cool it to 4° C. Higher or lower working temperatures may bepreferred as desired. Insulating material can be used to maintainoperating temperatures. The water bath 28 may include a thermometer 30and an alarm 31 to warn of dangerous operating temperatures.

Preferably a peristaltic pump 29 is used to circulate the liquid andpreferably it is positioned at a lower level than the pressure chamber4, thus letting gravitational forces, and the suction created by thepump, feed the pump. Because of this position of the pump 29, the amountof water going into the pressure chamber 4 always matches the volume ofwater coming into the pump 29, preventing pooling of water in thepressure chamber 4. By comparison, other pumps seemed to need a ratheradvance regulating system to match input/output.

Temperature sensors 32, 33 can record the skin temperature and tympanictemperature in the ear of the patient 1.

To generate negative pressure within the pressure chamber 4, valve B ofthe regulator 20 is open, connecting the interior of the pressurechamber 4 with the suction device 15. After a period of time, preferably10 seconds, valve B closes and valve A opens. Valve A bleeds air intothe pressure chamber 4, returning it to atmospheric pressure. The valveA remains open for a further period of time, preferably seconds. Valve Ais then closed and valve B opened to repeat the cycle.

FIG. 6 a shows an exploded view of the pressure application device 3used in FIG. 5. A jubilee clip 34 retains the neoprene seal 25 on thecarved POM extension piece 24.

To fit the pressure chamber 4 to the patient's arm 1, first the rubberseal 26, which is in the form of a tapered hose, is slid up the arm.Then the neoprene seal 25 with the extension piece 24 is slid onto thearm below the rubber seal 26. The arm 1 is then inserted into thepressure chamber and the extension piece 24 is attached to seal off thepressure chamber. The rubber seal 26 is rolled down over the neopreneseal 25, extension piece 24 and top of the pressure chamber 4 to ensureproper sealing. The pressure chamber 4 is then circulated with warm orcold water and pulses of pressure are generated within the pressurechamber 4.

FIGS. 7 a to 7 c show the pressure application device 3 operating atdifferent angles. The provision of two connection pieces 14 connected topressure lines 19 ensures that at least one of the connection pieces 14is located in the air gap 12. This is important as the patient 1 may bein a declined or inclined position to assist an operation.

FIGS. 8 a to 8 d show a pressure application device 3 that is adaptedfor use on a leg. Depending on the width of the knee, the mostappropriate size neoprene seal 25 a, 25 b, 25 c is chosen and fitted tothe patient. The rubber seal 26 would then fit over one end of theextension piece 24. As seen in FIG. 8 c, the pressure chamber 4comprises a cylindrical section 35 for the patient's leg and a boxsection 36 for the foot. The cylindrical section 35 would allow thedevice 3 to be rolled from side to side slightly to alleviate discomfortin the patient. In this embodiment, a single connection piece 14 isprovided for communication with the pressure source 15. An inlet 7 andoutlet 8 are provided at the base of the box section 36 for circulatingwater within the device 3.

FIG. 9 illustrates a further device 3 having a sleeve 37 of a flexiblematerial such as a latex membrane to provide a barrier between thecirculating water and the skin of the patient. Such a device might beused to avoid wrinkling of the skin. The sleeve 37 divides the pressurechamber 4 into two compartments; an inner compartment for receiving thelimb and an outer compartment for the circulated liquid. A connection 38is provided in communication with the inner compartment to create asmall negative pressure of preferably 0.5-1.0 mmHg of negative pressure(−0.065 to −0.13 kPa). This sucks the sleeve 37 into full contact withthe limb to ensure good thermal energy transfer. Pressure pulses areapplied to the circulating water through the connection to the outercompartment via pressure lines 19 in the normal way. The pressure in theouter compartment can be reduced accordingly, but this is probably notnecessary. Leaks are less likely and cleaning of the system is easier.

A similar flexible sleeve incorporating a heating element may also beused as a way of providing thermal energy to the patient (not shown).For such an arrangement an electric cable would need to be provided of asufficient length to allow the sleeve to be fitted to the patient priorto the patient inserting his arm into the pressure chamber 4.Alternatively some form of induction heating may be possible.

FIG. 10 illustrates the results of a comparison between the device ofthe present invention and a known system of forced air warming which ismarketed under the registered trade mark of “Bair Hugger”®. Bair Hugger®is made of blankets which cover whatever part of the body is not beingused in an operation. In abdominal surgery this can be a problem becausethe larger parts of the body, e.g., head, neck, abdomen and legs cannotbe warmed by the force air warmer because access is required for otheroperations. Abdominal surgery is also often long lasting e.g. more thantwo hours and patients developing hypothermia is a huge problem.Hypothermia can cause severe problems for patients including cardiacarrhythmia and increased risk of infection and ischemic heart disease.In the study a pressure application device as shown in FIG. 1 wasapplied to the patient's arm and this was found to be enough to keep thepatient warm.

In one additional test trial, a plexus anaesthesia was administered inthe left arm to block signals from thermoreceptors to the centralnervous system and thereby to decrease sympathetic activity to thevessels, preventing vasoconstriction. After inducing regionalanaesthesia the pressure within the chamber was pulsated and 10° C.water was circulated in the pressure chamber to induce hypothermia. Thepressure inside the chamber was pulsated between 0 and −40 mmHg (0 and−5.3 kPa). The core temperature decreased from 36.9° C. to 36.3° C. Toinduce anaesthesia the doctor used 40 ml 0.1% Xylocain. This did notgive a full regional anaesthesia of the arm and the subject started toshiver a little bit during the last part of the cooling. Full surgicalanaesthesia of the arm would be possible with pethidin so as to preventshivering. It is believed that if the same procedure were used onpatients in general anaesthesia it would probably have been even easierto induce hypothermia.

Measurement of blood flow was done using ultrasound Doppler and laserDoppler. In the preferred examples, the ultrasound Doppler technique wasused to Measure blood velocity (m/sec). If there is no change in vesseldiameter, the velocity is proportional to flow (volume/time). LaserDoppler was also used to record blood flow (a.u.) in the skin. Theregistrations were transferred to a computer by an A/D-card and sampledat 50 Hz. Using a simultaneous ECG recording, the velocities weresampled beat by beat. In another trial, computer was also used to openand close the valves, generating a pulsating pressure (10,11).

In an additional test trial, the effects of applying a local pulsatingnegative pressure on arterial blood velocities were studied. In the testtrial subjects were comfortably positioned on a bed in a supineposition, their right arm was abducted 70-90 degrees and positionedinside a custom built tube shaped transparent plexiglass chamber similarto the apparatus illustrated in FIG. 1. The chamber was sealed to theupper arm by a neoprene collar, which was attached to an adapter. Anelastic rubber hose covered the adapter/neoprene collar and continuedapproximately 5 cm on the arm and about 5 cm distally on the tube. Thechamber was connected to an adjustable medical suction device. A pair ofcomputer-controlled magnetic valves was connected between the chamberand the suction device, making it possible to control the pressureinside the chamber. Each experiment for each individual subject wasdivided into 3 periods, each consisting of a 2-minute measurement periodpreceded and followed by 1 minute baseline recordings (See FIG. 11).During each period, the pressure inside the chamber was either 0(=ambient pressure, −40, or pulsated between 0 and −40 mmHg. Pulsatingpressure was applied to the right arm (experimental arm) and no pressurewas applied to the left arm (control arm). The pressure applied to theright arm was pulsated in sequences of 10 seconds on and 7 seconds off.The order of periods in each experiment was randomized. Baselinerecording started when the brachial arterial blood flow showed largefluctuations indicating that the subjects were in their thermoneutralzone.

Blood velocity was measured using ultrasonic Doppler and laser Dopplermethods. The blood velocity of the right arm was measured from the rightaxillary artery and the velocity of the left arm was measured from theleft brachial artery. A bi-directional ultrasound Doppler velocimeter(SD-100, GE Vingmed Ultrasound, Horton Norway) was operated in thepulsed mode with a handheld 10 MHz probe. The ultrasound beam wasdirected at an angle of approximately 45° to the vessel on the medialside of the arm, about 5 cm distal to the axillary fossa. As previouslyindicated, as a control, blood velocity measurements were also made inthe left brachial artery. The SD-100 on the right hand side also had abuilt in three-lead surface electrocardiogram (ECG) which was attachedto the right and left shoulder and to the lower edge of the ribcage inthe left midclavicular line. Laser Doppler flux (LDF) was recorded fromthe pulpa of the second finger of the left arm (MBF3D; Moor Instruments,Devon, UK). In addition, instantaneous arterial blood pressure (BP) wasobtained from the left third finger using a photoplethysmographic device(Ohmeda 2300 Finapres, Madison, Wis.). The chamber pressure wasmonitored with a digital manometer (Piezoresistive Transmitter Serie 23,Keller A G, Switzerland). The readings from the instruments were fedonline to a personal computer and recorded at different frequencies. Thesame computer was preprogrammed to control the magnetic valves. Therecordings were displayed realtime on a computer screen.

Instantaneous cross sectional mean velocities from the axillary andbrachial arteries were calculated by the ultrasound Doppler Instruments,and together with the readings of LDF, BP and chamber pressure fedonline to a computer for beat by beat time averaging, gated by ECG Rwaves. The analog signals were converted to a digital signal andrecorded by the computer at 2 Hz and 50 Hz. The program calculated theheart rate (HR) based on the ECG signal.

FIGS. 11A-E show simultaneous recordings of chamber pressure, HR, BP andblood velocity in both arms from one subject. It shows blood velocityover time for the right (experimental) arm compared to the bloodvelocity over time for the left (control) arm. During the pulsatingphase, the blood velocity in the right axillary artery shows largefluctuations, which are synchronous with fluctuations in pressure. Atthe onset and end of constant negative pressure there are large changesin blood velocity. There is a short increase in blood velocity, lastingabout 15 seconds when the negative pressure is applied. At the withdrawof negative pressure there is a short lasting decrease in velocity. Thisis followed by another longer lasting, 15 second increase in velocitywith another increase in pressure. The blood velocity in the control armis at about the same value as baseline recordings in the opposite arm.There are no large changes in the velocities in the control arm. MAP andHR did not change during the experiment, a common finding to allexperimental runs. Thus, pulsating negative pressure causes an increasein blood velocity compared to normal pressure.

FIG. 12 A-C shows chamber pressure compared to relative blood velocitiesfrom each the right (experimental) arm and the left (control) arm duringnormal pressure, constant negative pressure and pulsating negativepressure. The first column depicts normal pressure, the second columndepicts constant negative pressure and the third column depictspulsating negative pressure. The average blood velocity in the right(experimental) arm is 47.4% higher when pulsating negative pressure isapplied compared to the average blood velocity under normal pressure.The average blood velocity is 16.9% higher when constant negativepressure is applied compared to the average blood velocity under normalpressure. The average blood velocity in the left (control) isapproximately the same in each of these. Thus, pulsating negativepressure causes a much higher increase in blood velocity than constantnegative pressure.

The present invention can also be used to cool down patients withhyperthermia. FIG. 13 shows the tympanic temperature of a patient withhyperthermia over time. A patient was exposed to 40-50° C. warm air andrelative humidity of 40% for 1-2 hours and became hypothermic with atympanic temperature of 38.5° C. The body temperature was initiallymeasured to 37.0° C. After the equipment was applied and registering onthe computer started the temperature had risen to 37.5° C. At point A inFIG. 13, the tympanic temperature had risen to 38.7° C. and sweating hadstarted. At point B, the tympanic temperature had risen to 38.5° C. andthe patient reported to become uncomfortable. An arm of the patient wasplaced in the chamber of one embodiment of the device of the presentinvention. The circulating water was set to 23° C. and pulsatingpressure was applied to the arm in sequences of 10 seconds at −40 mmHgand 7 seconds at 0 mmHg. The 40-50° C. warm air and relative humidity of40% were maintained during treatment. Forty minutes later, the tympanictemperature was reduced to 37.5° C. Thus, the present invention can beused to treat patients with hyperthermia.

Other possibilities envisaged within the present invention are makingthe pressure chamber 4 more anatomically correct; making a “one sizefits all” model; one or multi-piece; the provision of a “door” to putthe arm/leg into for easier access, etc. In addition to treatinghypothermia, the method may be used on many different clinical problems.Treating ischemic feet is one possibility: Another is treating large legulcers to avoid amputation. The possibilities are endless.

1. A device for applying a pulsating pressure to a local region of thebody, the device comprising a pressure chamber in to which a limb of thebody can be placed to seal it from external conditions, whereby in usethe limb can be immersed in a liquid contained in the pressure chambersuch that the liquid surrounds and is in contact with the limb whereinan element is provided to generate pulses of pressure within the chamberthat can be transmitted to the limb directly via the liquid.